Programmed ribosomal frameshifting during <i>PLEKHM2</i> mRNA decoding generates a constitutively active proteoform that supports myocardial function.

ABSTRACT: Programmed ribosomal frameshifting is a process where a proportion of ribosomes change their reading frame on an mRNA¹, rephasing the ribosome relative to the mRNA. While frameshifting is commonly employed by viruses², very few phylogenetically conserved examples are known in nuclear encoded genes and some of the evidence is controversial^3,4. Here we report a +1 frameshifting event during decoding of the human gene PLEKHM2 ⁵. This frameshifting occurs at the sequence UCC_UUU_CGG, which is conserved in vertebrates and is similar to an influenza virus sequence that frameshifts with similar efficiency^6,7. The new C-terminal domain generated by this frameshift forms an α-helix, which relieves PLEKHM2 from autoinhibition and allows i

SUBMITTER: Loughran G 

PROVIDER: S-EPMC11451614 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature